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PubMed1991

Trypsin activation of inactive renin: plasma blanks and angiotensin I radioimmunoassay.

Divergent conclusions exist as to whether inactive renin is present in nephrectomized rat plasma. A major factor contributing to this conflict may be related to significant changes in the "plasma blank" when trypsin-treated plasma is subjected to angiotensin I (AI) radioimmunoassay (RIA). In normal, but not nephrectomized rat plasma, AI-like substances are present in direct proportion to active renin. These substances are destroyed by trypsin. However, trypsin generates additional AI-like material, in both normal and nephrectomized rat plasma. This material, which is present in proportion to the renin substrate concentration, does not appear to be tetradecapeptide (TDP). In normal plasma, however, exogenous TDP is converted to AI in proportion to the active renin concentration and AI generation from TDP is increased by activation of inactive renin. However, in nephrectomized rat plasma, no AI generation from TDP was evident either before or after trypsin treatment. The coincident tryptic generation of a substance that quenches the levels of AI detected by RIA, combined with significant changes in the levels of endogenous and trypsin generated AI-like substances, may have significant bearing on the measured levels of inactive renin.

Amino Acid Sequence↗

PubMed2001

Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells.

Endothelial cells (EC) metabolize L-arginine mainly by arginase, which exists as two distinct isoforms, arginase I and II. To understand the roles of arginase isoforms in EC arginine metabolism, bovine coronary venular EC were stably transfected with the Escherichia coli lacZ gene (lacZ-EC, control), rat arginase I cDNA (AI-EC), or mouse arginase II cDNA (AII-EC). Western blots and enzymatic assays confirmed high-level expression of arginase I in the cytosol of AI-EC and of arginase II in mitochondria of AII-EC. For determining arginine catabolism, EC were cultured for 24 h in DMEM containing 0.4 mM L-arginine plus [1-(14)C]arginine. Urea formation, which accounted for nearly all arginine consumption by these cells, was enhanced by 616 and 157% in AI-EC and AII-EC, respectively, compared with lacZ-EC. Arginine uptake was 31-33% greater in AI-EC and AII-EC than in lacZ-EC. Intracellular arginine content was 25 and 11% lower in AI-EC and AII-EC, respectively, compared with lacZ-EC. Basal nitric oxide (NO) production was reduced by 60% in AI-EC and by 47% in AII-EC. Glutamate and proline production from arginine increased by 164 and 928% in AI-EC and by 79 and 295% in AII-EC, respectively, compared with lacZ-EC. Intracellular content of putrescine and spermidine was increased by 275 and 53% in AI-EC and by 158 and 43% in AII-EC, respectively, compared with lacZ-EC. Our results indicate that arginase expression can modulate NO synthesis in bovine venular EC and that basal levels of arginase I and II are limiting for endothelial syntheses of polyamines, proline, and glutamate and may have important implications for wound healing, angiogenesis, and cardiovascular function.

Animals↗

PubMed1980

Age-related differences in angiotensin I metabolism by isolated perfused rat lungs.

The pulmonary vasculature has been implicated in the clearance of several vasoactive substances from the circulation including angiotensin I (AI). In view of the previously reported age-related differences in angiotensin-converting enzyme (ACE) activity of lung homogenates, it was of interest to examine the ability of intact perfused lungs to metabolize AI. Lungs from newborn and adult rats were perfused with Krebs bicarbonate buffer containing 1.0 ng/ml AI in a single-pass, nonrecirculating system. The rate of perfusion was normalized to lung mass. Removal of AI was determined from the transpulmonary difference in radioimmunoassayable AI. Lungs from 7-day-old rats removed a smaller fraction of AI from the circulation than did adult lungs. The age-related increase in AI clearance was accompanied by an increase in pulmonary ACE content; however, enzyme content alone could not account for the observed differences. The increased metabolism of AI by the pulmonary vasculature during development may contribute to the age-related increase in circulating angiotensin II concentrations.

Aging↗

PubMed2004

Modular functional organization of cat anterior auditory field.

Two tonotopic areas, the primary auditory cortex (AI) and the anterior auditory field (AAF), are the primary cortical fields in the cat auditory system. They receive largely independent, concurrent thalamocortical projections from the different thalamic divisions despite their hierarchical equivalency. The parallel streams of thalamic inputs to AAF and AI suggest that AAF neurons may differ from AI neurons in physiological properties. Although a modular functional organization in cat AI has been well documented, little is known about the internal organization of AAF beyond tonotopy. We studied how basic receptive field parameters (RFPs) are spatially organized in AAF with single- and multiunit recording techniques. A distorted tonotopicity with an underrepresentation in midfrequencies (1 and 5 kHz) and an overrepresentation in the high-frequency range was found. Spectral bandwidth (Q-values) and response threshold were significantly correlated with characteristic frequency (CF). To understand whether AAF has a modular organization of RFPs, CF dependencies were eliminated by a nonparametric, local regression model, and the residuals (difference between the model and observed values) were evaluated. In a given isofrequency domain, clusters of low or high residual RFP values were interleaved for threshold, spectral bandwidth, and latency, suggesting a modular organization. However, RFP modules in AAF were not expressed as robustly as in AI. A comparison of RFPs between AAF and AI shows that AAF neurons were more broadly tuned and had shorter latencies than AI neurons. These physiological field differences are consistent with anatomical evidence of largely independent, concurrent thalamocortical projections in AI and AAF, which strongly suggest field-specific processing.

Acoustic Stimulation↗

PubMed1997

Modulatory effects of regional cortical activation on the onset responses of the cat medial geniculate neurons.

Corticofugal modulation on activity of the medial geniculate body (MGB) was examined by locally activating the primary auditory cortex (AI) and looking for effects on the onset responses of MGB neurons to acoustic stimuli. Of 103 MGB neurons recorded from 13 hemispheres of 11 animals, 91 neurons (88%) showed either a facilitatory or inhibitory effect or both; of these neurons, 72 showed facilitatory effects and 25 inhibitory effects. The average facilitatory effect was large, with a mean increase of 62.4%. Small inhibitory effects (mean: -16.2%) were obtained from a few neurons (6 of 103) when a pure tone stimulus was used, whereas the effect became larger and more frequent when a noise burst stimulus was used (mean: -27.3%, n = 22 of 27 neurons). Activation of an AI site having the same best frequency (BF) as the MGB neuron being recorded from produced mainly a facilitatory effect on MGB neuronal responses to pure tones. Activation of AI at a site neighboring the BF site produced inhibitory effects on the MGB response when noise burst stimuli were used. We found that the effective stimulation sites in AI that could modulate MGB activity formed patchlike maps with a diameter of 1.13 +/- 0.09 (SE) mm (range 0.6-1.9 mm, n = 15) being larger than the patches of thalamocortical terminal fields. Examining the effects of sound intensities, of 18 neurons tested 9 neurons showed a larger effect for low-sound-intensity stimuli and small or no effects for high-sound-intensity stimuli. These were named low-sound-intensity effective neurons. Five neurons showed high sound intensity effectiveness and four were non-intensity specific. Most low-sound-intensity effective neurons were monotonic rate-intensity function neurons. The AI cortical modulatory effect was frequency specific, because 15 of 27 neurons showed a larger facilitatory effect when a BF stimulus was used rather than a stimulus of any other frequency. The corticothalamic connection between the recording site in MGB and the most effective stimulation site in AI was confirmed by injecting wheat germ agglutinin-horseradish peroxidase tracer at the stimulation site and producing a small lesion in the recording site. The results suggest that 1) the large facilitation effects obtained by AI activation at the region that directly projected to the MGB could be the result mainly of the direct projection terminals to the MGB relay neurons; 2) the large size patches of the effective stimulation site in AI could be due to widely ramifying corticothalamic projections; and 3) the corticofugal projection selectively gates auditory information mainly by a facilitatory effect, although there is also an inhibitory effect that depends on the sound stimulus used.

Acoustic Stimulation↗

PubMed1997

First-spike timing of auditory-nerve fibers and comparison with auditory cortex.

First-spike timing of auditory-nerve fibers and comparison with auditory cortex. J. Neurophysiol. 78: 2438-2454, 1997. The timing of the first spike of cat auditory-nerve (AN) fibers in response to onsets of characteristic frequency (CF) tone bursts was studied and compared with that of neurons in primary auditory cortex (AI), reported previously. Tones were shaped with cosine-squared rise functions, and rise time and sound pressure level were parametrically varied. Although measurement of first-spike latency of AN fibers was somewhat compromised by effects of spontaneous activity, latency was an invariant and inverse function of the maximum acceleration of peak pressure (i.e., a feature of the 2nd derivative of the stimulus envelope), as previously found in AI, rather than of tone level or rise time. Latency-acceleration functions of all AN fibers were of very similar shape, similar to that observed in AI. As in AI, latency-acceleration functions of different fibers were displaced along the latency axis, reflecting differences in minimum latency, and along the acceleration axis, reflecting differences in sensitivity to acceleration [neuronal transient sensitivity (S)]. S estimates increased with spontaneous rate (SR), but values of high-SR fibers exceeded those in AI. This suggests that S estimates are biased by SR per se, and that unbiased true S values would be less tightly correlated with response properties covarying with SR, such as firing threshold. S estimates varied with CF in a fashion similar to the cat's audiogram and, for low- and medium-SR fibers, matched those for AI neurons. Minimum latency decreased with increasing SR and CF. As in AI, the standard deviation of first-spike timing (SD) in AN was also an inverse function of maximum acceleration of peak pressure. The characteristics of the increase of SD with latency in a given AN fiber/AI neuron and across AN fibers/AI neurons revealed that the precision of first-spike timing to some stimuli can actually be higher in AI than in AN. The data suggest that the basic characteristics of the latency-acceleration functions of transient onset responses seen in cortex are generated at inner hair cell-AN fiber synapses. Implications for signal processing in the auditory system and for first-spike generation and adaptation in AN are discussed.

Acoustic Stimulation↗

PubMed2004

Sequencing of endocrine therapy in postmenopausal women with advanced breast cancer.

The introduction of the nonsteroidal aromatase inhibitor (NS-AI) anastrozole as an alternative to tamoxifen for adjuvant therapy of women with resected hormone receptor-positive breast cancer has added a management category into which patients presenting with metastatic disease can be placed. There are now essentially three such categories: (a) tamoxifen sensitive (no prior AI); (b) tamoxifen resistant (no prior AI); and (c) NS-AI resistant (no prior tamoxifen). Well-conducted Phase III trials provide evidence for choosing first-line therapy for advanced disease in categories a and b. In tamoxifen-sensitive patients, one can choose either NS-AI, anastrozole, or letrozole. In tamoxifen-resistant patients, one can choose either of the NS-AIs, the steroidal AI exemestane, or the estrogen receptor down-regulator fulvestrant. The situation is quite different for patients in category c. There are no Phase III trials of agents in patients who have experienced disease progression on a NS-AI. Phase II data are available for exemestane and high-dose estrogens, and retrospective data are available for tamoxifen and fulvestrant. Additional clinical trials are needed to determine an optimal sequencing strategy.

Androstadienes↗

PubMed2005

Allelic imbalance in primary breast carcinomas and metastatic tumors of the axillary lymph nodes.

Axillary lymph node status is the most important prognostic factor in predicting disease outcome in women with breast cancer. A number of chromosomal aberrations in primary breast tumors have been correlated with lymph node status and clinical outcome, but chromosomal changes particular to metastatic lymph node tumors have not been well studied. DNA samples isolated from laser-microdissected primary breast and metastatic axillary lymph node tumors from 25 women with invasive breast cancer were amplified using 52 microsatellite markers defining 26 chromosomal regions commonly deleted in breast cancer. Levels and patterns of allelic imbalance (AI) within and between breast and lymph node tumors were assessed to identify chromosomal alterations unique to primary or metastatic tumors and to examine the timing of metastatic potential. The overall frequency of AI in primary breast tumors (0.24) was significantly greater (P < 0.001) than that in lymph node tumors (0.10), and congruent AI events were observed for < 20% of informative markers. AI at chromosomes 11q23.3 and 17p13.3 occurred significantly more frequently (P < 0.05) in primary breast tumors alone; no chromosomal regions showed a significantly higher AI frequency in lymph nodes. Higher rates of AI in primary versus metastatic lymph node tumors suggest that acquisition of metastatic potential may be an early event in carcinogenesis, occurring before significant levels of AI accumulate in the primary tumor. In addition, patterns of AI were highly discordant between tumor types, suggesting that additional genetic alterations accumulated independently in the two cell populations.

Allelic Imbalance↗

PubMed2004

High apoptotic index correlates to p21 and p27 expression indicating a favorable outcome of primary breast cancer patients, but lacking prognostic significance in multivariate analysis.

This study was performed in order to investigate the role of the apoptotic index (AI) as a prediction parameter for the prognosis of patients with primary breast cancer. AI was determined by DNA fragmentation on 298 primary breast cancer samples and compared to clinically established breast cancer parameters. Additionally, we determined the expression of functional parameters including proliferating cell nuclear antigen, p21waf and p27kip by immunohistochemistry. The mean AI was found to be 11.9% (range, 0-90%). 189 tumors (63.4%) were negative for apoptosis, while 109 tissue samples (36.6%) were apoptotic with >5% positive cells. Using univariate analysis (chi2 test), the AI did not show any significant correlation to one of the established prognostic parameters of primary breast cancer (p > 0.05). In contrast, we found a significant positive correlation to the expression of the cell cycle inhibitors p21waf (p = 0.04) and p27kip (p = 0.024). During the clinical follow-up (median observation time for disease-free survival 87 months), several clinically established prognostic parameters including menopausal status, nodal status, tumor size, tumor grade, and hormone receptor expression could be confirmed and were analyzed with respect to the AI in the tumor. Furthermore, AI displayed a significant positive correlation to disease-free survival using Kaplan-Meier survival analysis (log-rank test, p = 0.04). However, AI lost its prognostic significance in multivariate analysis based on the Cox proportional hazard model (relative risk 0.8, confidence interval 0.52-1.33, p = 0.44). Our data indicate that high apoptotic rates in cancer tissues are indicative of a favorable patient outcome. However, the AI was not an independent factor. The study provides indirect evidence that this process may involve cell cycle inhibitors physiologically.

Apoptosis↗

PubMed2006

Activity Index - a complementary ADL scale to the Barthel Index in the acute stage in patients with severe stroke.

OBJECTIVE: It was the aim of this study to compare the Barthel Index (BI) and the activities of daily living (ADL) component of the Activity Index [AI(ADL)] regarding floor and ceiling effects, responsiveness and the predictive value for survival during the first week until 3 months after stroke onset. PATIENTS AND METHODS: Basic ADL were assessed in 75 patients with ischaemic stroke. RESULTS: There was a strong concordance between BI and AI(ADL) scores at all time points (Kendall's taub = 0.7878, p < 0.0001 at baseline; Kendall's taub = 0.8901, p < 0.0001 at 1 week; Kendall's taub = 0.9027, p < 0.0001 at 3 months). BI had a significantly more pronounced floor effect at baseline and at 1 week compared with AI(ADL) in patients with severe stroke. Both scales had a substantial ceiling effect at 3 months. At 1 week, the baseline BI score was significantly higher in patients being alive as compared with those who had died, while their AI(ADL) score did not differ significantly. At 3 months, baseline BI and AI(ADL) scores were significantly higher in patients being alive as compared with those who had died. The predictive value of being alive at 1 week and 3 months did not differ between BI and AI(ADL). CONCLUSION: AI(ADL) is recommended to be used in addition as a complement to BI in patients with severe stroke since the floor effect with BI in the acute stage is significantly more pronounced than with AI(ADL), thus hampering the responsiveness.

Activities of Daily Living↗

PubMed1979

'Minor hemoglobins': an alternative approach for evaluating glucose control in pregnancy.

'Minor hemoglobins' (Hb AI) were measured in 178 women during pregnancy and immediately postpartum by a thiobarbituric acid spectrophotometric method. The patients were classified according to an oral glucose tolerance test (GTT) and an assessment of risk factors for diabetes in normal (n = 75), probably normal (n = 72) and chemical diabetics (n = 26). 5 pregnant insulin-dependent diabetics were also studied. Hb AI was unchanged during the second and third trimesters of pregnancy and immediately postpartum (less than 6 days) in women with normal glucose tolerance. Moreover, no difference of Hb AI level was found when compared with a separate group of nonpregnant individuals (n = 15). Chemical diabetics had significantly higher mean third trimester and postpartum Hb AI than normals (p less than 0.001). The highest Hb AI levels during pregnancy were found in the insulin-dependent diabetics, although these were lower compared to a separate group of nonpregnant insulin-dependent diabetics (n = 10; p less than 0.05). During pregnancy, a significant correlation was found between Hb AI and the 2-hour value of the GTT (p less than 0.001). A positive correlation was also found between third trimester maternal Hb AI and infant birth weight (p less than 0.001). Hb AI may complement other parameters in evaluating maternal glucose tolerance during pregnancy.

Birth Weight↗

PubMedDate not supplied

Atypical glandular cells of undetermined significance in cervical smears after conization. Cytologic features differentiating them from adenocarcinoma in situ.

OBJECTIVE: To evaluate the cytologic features of atypical glandular cells of undetermined significance (AGUS) smears following conization through a comparison with adenocarcinoma in situ (AIS) smears. STUDY DESIGN: Fifty cervical smears, diagnosed as AGUS based on groups of crowded glandular cells that raised the possibility of AIS, from 38 patients who had conization and 24 AIS smears, histologically confirmed, from 17 patients were reviewed. Subsequent follow-up biopsies or hysterectomies in 38 patients were evaluated. RESULTS: Nuclear atypia was a more reliable feature than architectural structure in differentiating postcone effect from AIS on cytology. The predominant cytologic features of the postcone smears were crowded glandular cells with a high nuclear/cytoplasmic ratio and relatively small, hyperchromatic nuclei with rather finely granular and uniformly dispersed chromatin, less distinct nuclear membranes, less frequent mitosis and presence of endometrial-type stromal cells in the background. The architecture of the crowded cells in the postcone smears was sometimes similar to that of AIS. No AIS or high grade squamous intraepithelial lesion histology was encountered in follow-up biopsies or hysterectomy specimens. CONCLUSION: The cytologic features distinguishing AGUS from AIS may be helpful in identifying the postcone effect. Since it is important to avoid miscalling the postcone effect as AIS, it is recommended that one check for a previous history of a cone biopsy.

Adenocarcinoma↗

PubMed1995

Severe familial HDL deficiency in French-Canadian kindreds. Clinical, biochemical, and molecular characterization.

A decreased level of HDL cholesterol (HDL-C) is the most common lipoprotein abnormality seen in people with premature coronary artery disease (CAD). In many cases, HDL-C reduction in patients with CAD may be the result of increased apo B-containing lipoprotein production by the liver with secondary hypoalphalipoproteinemia. Primary hypoalphalipoproteinemia is seen in approximately 4% of people with CAD. We report findings in four subjects with severe familial HDL deficiency (HDL-C << 5th percentile for age and sex; 0.08 to 0.38 mmol/L) in three French-Canadian kindreds with autosomal codominant inheritance. By inclusion criteria, all four subjects had normal fasting triglycerides and none were diabetic. HDL particle size by gradient gel electrophoresis revealed small HDL particles (estimated Stokes' diameter, 8.14 to 8.30 nm). Apo AI analysis by polyacrylamide gel electrophoresis and use of isoelectrofocusing gels in affected subjects revealed normal molecular weight (28.3 kD) and normal isoelectrofocusing point but a relative increase in proapoliprotein AI, with near-normal levels of proapolipoprotein AI in plasma, suggesting normal secretion of apo AI. Quantitative Southern blot analysis of the apo AI-CIII-AIV gene cluster reveals no gene rearrangements or allele deletion. Haplotypes of the apo AI gene, determined by use of the restriction enzymes Pst I, Xmn I, and Sst I and of the apo AII gene by use of the enzyme Msp I, did not reveal segregation of the low HDL-C trait with either the apo AI or the AII gene. Sequence analysis of the promoter region of the apo AI gene reveals heterozygosity for guanine-to-adenine substitution at position 76 in two kindreds with no evidence of segregation with the low HDL trait. None of the patients had mutations of the lipoprotein lipase gene common in subjects of French-Canadian descent. Haplotype analysis of the lipoprotein lipase gene did not show segregation with the low HDL trait. Plasma lecithin: cholesterol acyltransferase (LCAT) activity was found to be within normal levels in affected subjects and in nonaffected first-degree relatives. None of the affected subjects had clinical manifestations of Tangier disease. Two of the four cases examined, both men, had severe CAD and had undergone revascularization procedures. The third is a younger brother of one of these probands and the fourth is a 30-year-old woman, and both were free of clinical CAD. However, in none of the families did the low HDL trait unequivocally cosegregate with CAD.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1996

Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure.

Our objective was to validate a carotid artery tonometry-derived augmentation index as a means to estimate augmentation index (AI) of ascending aortic pressure under various physiological conditions. A total of 66 patients (50 men, 16 women; mean age, 55 years; range, 21 to 78 years; 44 in Taiwan and 22 in the United States) undergoing diagnostic catheterization were studied. Arterial pressure contours were obtained simultaneously from the right common carotid artery by applanation tonometry with an external micromanometer-tipped probe and from the ascending aorta by a micromanometer-tipped catheter at baseline (n = 62), after handgrip (n = 36), or after sublingual nitroglycerin administration (n = 17). The AI (expressed as percentage values) was calculated as the ratio of amplitude of the pressure wave above its systolic shoulder to the total pulse pressure. The carotid AI was consistently lower than the aortic AI, but the two were highly correlated at baseline and after both handgrip and nitroglycerin. Mean +/- SD and correlation coefficients were baseline (14 +/- 16, 28(+) +/- 17, .77), handgrip (18 +/- 19, 32(+) +/- 15, .86), and nitroglycerin (7 +/- 12, 18(+) +/- 13, .52). In addition, after adjusting for age, sex, height, blood pressure, heart rate, and study site, the changes of both AIs from baseline values with handgrip or nitroglycerin were highly associated such that the aortic AI could be approximated from the carotid AI with appropriate regression equations. The high correlations and predictable changes after interventions between the central AI and those estimated from noninvasive carotid tonometry suggest that this technique may have wide applicability for many cardiovascular studies.

Adolescent↗

PubMedDate not supplied

Angiotensin I, II, and II tachyphylaxis in the mesenteric vascular circuit of the rat.

Angiotensin tachyphylaxis is rapidly induced in the mesenteric vascular circuit of the rat perfused with a saline solution. there is crossed tachyphylaxis among angiotensins (AI, AII, and AIII). The angiotensin antagonist Sar 1-Ileu 8-AII is ineffective when the vascular preparation is previously rendered tachyphylactic to AII, showing that the AII receptors are not available during tachyphylaxis. This finding supports the theory that angiotensin tachyphylaxis is caused by receptor occupancy by the agonist. By perfusing the vascular preparation with aII solutions that were too diluted to produce vasoconstriction, tachyphylaxis to AII was induced. Therefore, AII receptors can be slowly saturated without producing vasoconstriction. The recoveries of the vasoconstrictor effect of AII and AIII at 30 and 60 minutes after tachyphylaxis are similar; thus, the dissociation constants of the AII- and AIII-receptor complexes should be alike. After three bolus injections of AI, the vascular preparation is completely refractory to AI, AII, and AIII. When the conversion of AI to AII is inhibited with captopril, AI no longer induces tachyphylaxis to AII and AIII. Thus, tachyphylaxis to AII and AIII induced by AI seems to be due not to the occupancy of AII receptors by AI but to the AII formation from AI "in situ."

Angiotensin I↗

PubMed2002

Paraoxonase 192 Gln-->Arg polymorphism: an independent risk factor for nonfatal arterial ischemic stroke among young adults.

BACKGROUND AND PURPOSE: The etiology of arterial ischemic stroke (AIS) in the young remains unknown in one third of patients. Serum paraoxonase (PON1) is an HDL-associated esterase that hydrolyzes products of lipid peroxidation and prevents the oxidation of LDL. Two common polymorphisms in the PON1 gene, the 192 Gln (Q) --> Arg (R) and 55 Leu (L) --> Met (M) substitutions, determine interindividual variation in PON1 activity. The association of these polymorphisms with the risk of AIS remains controversial. METHODS: We analyzed 118 patients (64 women) with a first nonfatal AIS occurring <45 years of age and 118 1:1 age (+/-2 years)- and sex-matched controls. The PON1 polymorphisms were determined by polymerase chain reaction amplification and restriction digestion. RESULTS: The prevalence of the PON1 192RR genotype (P=0.006) and the frequency of the R allele (P=0.010) were significantly increased among young AIS patients compared with controls. After adjustment for conventional vascular and prothrombotic risk factors, the 192RR genotype remained independently associated with a 4-fold increase in the risk of AIS (odds ratio=4.1; 95% CI, 1.14 to 14.73). Subanalyses stratified by the presence of vascular risk factors and ethnicity did not significantly modify the effect of the PON1 192 polymorphism on AIS risk. No significant differences were found between patients and controls regarding the PON1 55 polymorphism. CONCLUSIONS: These findings suggest that the PON 192RR genotype is independently associated with an increased risk of nonfatal AIS among young adults. Further studies are necessary to understand better the mechanistic implications of these observations in the development of AIS in the young.

Adult↗

PubMed1999

Safety of air medical transportation after tissue plasminogen activator administration in acute ischemic stroke.

BACKGROUND AND PURPOSE: We sought to determine the safety of air medical transport (AMT) of patients with acute ischemic stroke (AIS) immediately after or during administration of tissue plasminogen activator (tPA). Patients with AIS treated with tPA in nonuniversity hospitals frequently need transfer to tertiary care centers that can provide specialized care. AMT is a widely available mode of transport that is crucial in providing expedient and quality health care to critically ill patients while assuring high level of care during transportation. The safety of AMT of patients with AIS after or during administration of tPA has not been examined. METHODS: We performed retrospective chart review of 24 patients with AIS who were treated with intravenous tPA and transferred by helicopter to the Hospital of the University of Pennsylvania or the University of Cincinnati Hospital. The charts were reviewed for neurological complications, systemic complications, and adherence to the National Institutes of Neurological Disorders and Stroke (NINDS) protocol for AIS management. RESULTS: No major neurological or systemic complications occurred. Four patients had hypertension warranting treatment, 3 patients experienced motion sickness, 1 patient developed a transient confusional state, and 1 patient experienced minor systemic bleeding. Four NINDS protocol violations occurred, all related to blood pressure management. CONCLUSIONS: In this small series, AMT of AIS patients after thrombolysis was not associated with any major neurological or systemic complications. Flight crew education on the NINDS AIS protocol is essential in limiting the number of protocol violations. AMT of patients with AIS provides fast and safe access to tertiary centers that can provide state of the art stroke therapy.

Acute Disease↗

PubMed1988

Adrenaline-induced changes in serum electrolytes, ECG, and blood pressure, with Ca-blockade pretreatment.

Adrenaline infusions (AI) (0.5 micrograms adrenaline per 10 kg body weight per minute over 120 minutes) were given weekly for three weeks to 20 healthy male volunteers aged twenty-one to thirty-eight years. The AI was given after three days' treatment with diltiazem (D), verapamil (V), or placebo (PI) in a single-blind fashion. After pretreatment with Pl, serum potassium (s-K) decreased from 3.93 +/- 0.30 mmol/L (M +/- SD) to 3.33 +/- 0.31 (P less than 0.001) with the greatest change 69.75 +/- 46.24 minutes after the start of the AI. Corresponding values for s-Mg were 0.84 +/- 0.06 to 0.78 +/- 0.05 (P less than 0.01) and 106.50 +/- 36.71 minutes, for s-Ca 2.40 +/- 0.07 to 2.30 +/- 0.08 (P less than 0.01) and 103.50 +/- 36.06 minutes, for s-P 1.05 +/- 0.17 to 0.91 +/- 0.17 (P less than 0.02) and 80.25 +/- 47.25 minutes, and for s-urate 344.79 +/- 50.55 to 329.26 +/- 47.80 (P greater than 0.05) and 63.95 +/- 46.05 minutes. After pretreatment with D, AI produced similar electrolyte changes as after Pl, but the rise in blood glucose was slightly more pronounced and the drop in s-urate less pronounced. The heart rate (HR) before AI after pretreatment with D was lower than after Pl, but the increase during the AI was of the same magnitude. The AI-induced changes in systolic (SBP) and diastolic (DBP) blood pressure after D did not differ significantly from those seen after Pl, and neither did QT and QTc, whereas the PR duration was prolonged (0.18 +/- 0.03 second) when compared with Pl (0.16 +/- 0.02) (P less than 0.05). Although the magnitude of the change in DBP was not influenced, V prolonged the time till the lowest DBP (48.95 +/- 26.38 minutes) when compared with Pl (31.50 +/- 29.16 minutes) (P greater than 0.05). The other variables followed the same pattern as for D. In conclusion AI in healthy volunteers produced a drop in s-K but in addition a drop in s-Mg and s-Ca, the latter appearing later than the drop in s-K. Pretreatment with diltiazem and verapamil did not influence the magnitude of these changes but reduced the drop in s-urate.

Adult↗